CA2626921C - Procede et intermediaires pour la synthese de la caspofungine - Google Patents

Procede et intermediaires pour la synthese de la caspofungine Download PDF

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Publication number: CA2626921C
Authority: CA; Canada
Prior art keywords: formula; compound; alkyl; acid addition; addition salt
Prior art date: 2005-11-15
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA2626921A

Other languages

English (en)

Other versions

CA2626921A1 (fr

Inventor

Johannes Ludescher

Ingolf Macher

Ole Storm

Stephan Bertel

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Sandoz AG

Original Assignee

Sandoz AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2005-11-15

Filing date

2006-11-13

Publication date

2013-09-17

2006-11-13 Application filed by Sandoz AG filed Critical Sandoz AG

2007-05-24 Publication of CA2626921A1 publication Critical patent/CA2626921A1/fr

2013-09-17 Application granted granted Critical

2013-09-17 Publication of CA2626921C publication Critical patent/CA2626921C/fr

Status Expired - Fee Related legal-status Critical Current

2026-11-13 Anticipated expiration legal-status Critical

Links

238000000034 method Methods 0.000 title claims abstract description 66
JYIKNQVWKBUSNH-WVDDFWQHSA-N caspofungin Chemical compound C1([C@H](O)[C@@H](O)[C@H]2C(=O)N[C@H](C(=O)N3CC[C@H](O)[C@H]3C(=O)N[C@H](NCCN)[C@H](O)C[C@@H](C(N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N2)[C@@H](C)O)=O)NC(=O)CCCCCCCC[C@@H](C)C[C@@H](C)CC)[C@H](O)CCN)=CC=C(O)C=C1 JYIKNQVWKBUSNH-WVDDFWQHSA-N 0.000 title claims abstract description 28
229960003034 caspofungin Drugs 0.000 title claims abstract description 28
108010020326 Caspofungin Proteins 0.000 title claims abstract description 24
239000000543 intermediate Substances 0.000 title abstract description 22
230000015572 biosynthetic process Effects 0.000 title description 3
238000003786 synthesis reaction Methods 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 174
238000004519 manufacturing process Methods 0.000 claims abstract description 20
150000003839 salts Chemical class 0.000 claims description 87
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 56
239000002253 acid Substances 0.000 claims description 46
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 35
125000003342 alkenyl group Chemical group 0.000 claims description 34
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 31
239000012453 solvate Substances 0.000 claims description 30
229910052739 hydrogen Inorganic materials 0.000 claims description 17
238000002360 preparation method Methods 0.000 claims description 17
239000012024 dehydrating agents‎ Substances 0.000 claims description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 11
125000000623 heterocyclic group Chemical group 0.000 claims description 11
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
239000003054 catalyst Substances 0.000 claims description 8
MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 4
-1 caspofungin Chemical class 0.000 abstract description 10
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 4
125000004093 cyano group Chemical group *C#N 0.000 abstract 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 57
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
239000000203 mixture Substances 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 20
229960000583 acetic acid Drugs 0.000 description 19
238000006722 reduction reaction Methods 0.000 description 19
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
125000000217 alkyl group Chemical group 0.000 description 16
239000000047 product Substances 0.000 description 14
229910052799 carbon Inorganic materials 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
229940093499 ethyl acetate Drugs 0.000 description 10
235000019439 ethyl acetate Nutrition 0.000 description 10
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
DQXPFAADCTZLNL-FXDJFZINSA-N pneumocandin B0 Chemical compound C1([C@H](O)[C@@H](O)[C@H]2C(=O)N[C@H](C(=O)N3CC[C@H](O)[C@H]3C(=O)N[C@H](O)[C@H](O)C[C@@H](C(N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N2)[C@@H](C)O)=O)NC(=O)CCCCCCCC[C@@H](C)C[C@@H](C)CC)[C@H](O)CC(N)=O)=CC=C(O)C=C1 DQXPFAADCTZLNL-FXDJFZINSA-N 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
125000003277 amino group Chemical group 0.000 description 8
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000012535 impurity Substances 0.000 description 7
239000010948 rhodium Substances 0.000 description 7
239000007858 starting material Substances 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
108010049047 Echinocandins Proteins 0.000 description 6
238000003556 assay Methods 0.000 description 6
239000000243 solution Substances 0.000 description 6
239000002904 solvent Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 5
239000000463 material Substances 0.000 description 5
239000007787 solid Substances 0.000 description 5
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
239000000725 suspension Substances 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
LOOZZTFGSTZNRX-VIFPVBQESA-N L-Homotyrosine Chemical group OC(=O)[C@@H](N)CCC1=CC=C(O)C=C1 LOOZZTFGSTZNRX-VIFPVBQESA-N 0.000 description 3
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical class O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
150000007854 aminals Chemical group 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 3
238000002955 isolation Methods 0.000 description 3
125000002560 nitrile group Chemical group 0.000 description 3
230000000269 nucleophilic effect Effects 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
150000003140 primary amides Chemical group 0.000 description 3
238000000746 purification Methods 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000011946 reduction process Methods 0.000 description 3
229910052703 rhodium Inorganic materials 0.000 description 3
YXIWHUQXZSMYRE-UHFFFAOYSA-N 1,3-benzothiazole-2-thiol Chemical compound C1=CC=C2SC(S)=NC2=C1 YXIWHUQXZSMYRE-UHFFFAOYSA-N 0.000 description 2
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
208000030507 AIDS Diseases 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
239000005695 Ammonium acetate Substances 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
108010069514 Cyclic Peptides Proteins 0.000 description 2
102000001189 Cyclic Peptides Human genes 0.000 description 2
206010017533 Fungal infection Diseases 0.000 description 2
241001460671 Glarea lozoyensis Species 0.000 description 2
238000010268 HPLC based assay Methods 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
206010061598 Immunodeficiency Diseases 0.000 description 2
208000031888 Mycoses Diseases 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
241000233872 Pneumocystis carinii Species 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
229940043376 ammonium acetate Drugs 0.000 description 2
235000019257 ammonium acetate Nutrition 0.000 description 2
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
FAUOJMHVEYMQQG-HVYQDZECSA-N echinocandin B Chemical compound C1([C@H](O)[C@@H](O)[C@H]2C(=O)N[C@H](C(=O)N3C[C@H](C)[C@H](O)[C@H]3C(=O)N[C@H](O)[C@H](O)C[C@@H](C(N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N2)[C@@H](C)O)=O)NC(=O)CCCCCCC\C=C/C\C=C/CCCCC)[C@@H](C)O)=CC=C(O)C=C1 FAUOJMHVEYMQQG-HVYQDZECSA-N 0.000 description 2
108010062092 echinocandin B Proteins 0.000 description 2
239000003480 eluent Substances 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
239000010410 layer Substances 0.000 description 2
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
229960003104 ornithine Drugs 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
BJBUEDPLEOHJGE-UHFFFAOYSA-N (2R,3S)-3-Hydroxy-2-pyrolidinecarboxylic acid Natural products OC1CCNC1C(O)=O BJBUEDPLEOHJGE-UHFFFAOYSA-N 0.000 description 1
UHPDQDWXMXBLRX-DMTCNVIQSA-N (2s,3r)-2,5-diamino-3-hydroxypentanoic acid Chemical compound NCC[C@@H](O)[C@H](N)C(O)=O UHPDQDWXMXBLRX-DMTCNVIQSA-N 0.000 description 1
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical class C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
BJBUEDPLEOHJGE-BKLSDQPFSA-N 3-hydroxy-L-proline Chemical compound OC1CCN[C@@H]1C(O)=O BJBUEDPLEOHJGE-BKLSDQPFSA-N 0.000 description 1
NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 description 1
241000228212 Aspergillus Species 0.000 description 1
241000335423 Blastomyces Species 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
241000222120 Candida <Saccharomycetales> Species 0.000 description 1
241000223203 Coccidioides Species 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
230000005526 G1 to G0 transition Effects 0.000 description 1
241000228402 Histoplasma Species 0.000 description 1
241000283162 Inia geoffrensis Species 0.000 description 1
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
108010028921 Lipopeptides Proteins 0.000 description 1
241000144175 Lophium arboricola Species 0.000 description 1
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
229910019020 PtO2 Inorganic materials 0.000 description 1
KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000012296 anti-solvent Substances 0.000 description 1
229940121375 antifungal agent Drugs 0.000 description 1
239000003429 antifungal agent Substances 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
150000001504 aryl thiols Chemical class 0.000 description 1
125000001743 benzylic group Chemical group 0.000 description 1
238000012925 biological evaluation Methods 0.000 description 1
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
238000011210 chromatographic step Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
229910000071 diazene Inorganic materials 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
239000012467 final product Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000009776 industrial production Methods 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 description 1
239000011707 mineral Substances 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
239000002516 radical scavenger Substances 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
238000009666 routine test Methods 0.000 description 1
229910052707 ruthenium Inorganic materials 0.000 description 1
229930000044 secondary metabolite Natural products 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
BJBUEDPLEOHJGE-IMJSIDKUSA-N trans-3-hydroxy-L-proline Chemical compound O[C@H]1CC[NH2+][C@@H]1C([O-])=O BJBUEDPLEOHJGE-IMJSIDKUSA-N 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
AVCVDUDESCZFHJ-UHFFFAOYSA-N triphenylphosphane;hydrochloride Chemical compound [Cl-].C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 AVCVDUDESCZFHJ-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
- C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
- C07K7/56—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation not occurring through 2,4-diamino-butanoic acid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Biochemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Analytical Chemistry (AREA)
Public Health (AREA)
Communicable Diseases (AREA)
Animal Behavior & Ethology (AREA)
Oncology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CA2626921A 2005-11-15 2006-11-13 Procede et intermediaires pour la synthese de la caspofungine Expired - Fee Related CA2626921C (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP05024961.4		2005-11-15
EP05024961A EP1785432A1 (fr)	2005-11-15	2005-11-15	Procédé et produits intermédiaires pour la synthèse du caspofungin.
PCT/EP2006/010867 WO2007057141A1 (fr)	2005-11-15	2006-11-13	Procede et intermediaires pour la synthese de la caspofungine

Publications (2)

Publication Number	Publication Date
CA2626921A1 CA2626921A1 (fr)	2007-05-24
CA2626921C true CA2626921C (fr)	2013-09-17

Family

ID=36001076

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2626921A Expired - Fee Related CA2626921C (fr)	2005-11-15	2006-11-13	Procede et intermediaires pour la synthese de la caspofungine

Country Status (17)

Country	Link
US (1)	US20080319162A1 (fr)
EP (2)	EP1785432A1 (fr)
JP (1)	JP4966314B2 (fr)
KR (1)	KR101342304B1 (fr)
CN (1)	CN101305018B (fr)
AT (1)	ATE435233T1 (fr)
BR (1)	BRPI0618591A2 (fr)
CA (1)	CA2626921C (fr)
DE (1)	DE602006007612D1 (fr)
DK (1)	DK1951747T3 (fr)
ES (1)	ES2327962T3 (fr)
HR (1)	HRP20090474T1 (fr)
IL (1)	IL190333A (fr)
PL (1)	PL1951747T3 (fr)
PT (1)	PT1951747E (fr)
SI (1)	SI1951747T1 (fr)
WO (1)	WO2007057141A1 (fr)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
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WO2008012310A1 (fr)	2006-07-26	2008-01-31	Sandoz Ag	Préparations à base de caspofungine
US20090291996A1 (en) *	2008-05-21	2009-11-26	Ferenc Korodi	Caspofungin free of caspofungin Co
US8048853B2 (en)	2008-06-13	2011-11-01	Xellia Pharmaceuticals Aps	Process for preparing pharmaceutical compound and intermediates thereof
WO2010008493A2 (fr) *	2008-06-25	2010-01-21	Teva Gyógyszergyár Zártkörüen Müködö Részvénytársaság	Procédés pour préparer des azacyclohexapeptides de pureté élevée
US20090324635A1 (en) *	2008-06-25	2009-12-31	Ferenc Korodi	Caspofungin free of caspofungin impurity A
TW201024322A (en) *	2008-12-31	2010-07-01	Chunghwa Chemical Synthesis & Biotech Co Ltd	Preparation method for nitrogen containing heterocyclic hexapeptide with high conversion rate
WO2010108637A1 (fr)	2009-03-27	2010-09-30	Axellia Pharmaceuticals Aps	Composé cristallisé
WO2011014990A1 (fr) *	2009-08-06	2011-02-10	上海天伟生物制药有限公司	Azacyclohexapeptide ou son sel pharmaceutiquement acceptable, procédé de préparation et utilisation afférente
CN106397543A (zh) *	2010-09-28	2017-02-15	中化帝斯曼制药有限公司荷兰公司	用于分离环六肽的方法
CN102367269B (zh)	2010-11-10	2013-11-06	上海天伟生物制药有限公司	一种卡泊芬净类似物及其制备方法和用途
CN102367267B (zh)	2010-11-10	2013-09-04	上海天伟生物制药有限公司	一种卡泊芬净的制备方法
CN102367268B (zh)	2010-11-10	2013-11-06	上海天伟生物制药有限公司	一种卡泊芬净类似物及其用途
KR101331984B1 (ko)	2010-12-09	2013-11-25	종근당바이오 주식회사	카스포펀진 제조방법 및 그의 신규 중간체
CN102219833A (zh) *	2011-04-18	2011-10-19	深圳市健元医药科技有限公司	一种更加安全的棘白菌类抗真菌药的制备方法
CN102746384B (zh)	2011-04-22	2016-01-20	上海天伟生物制药有限公司	一种高纯度的卡泊芬净或其盐及其制备方法和用途
AU2012248013B2 (en)	2011-04-28	2016-07-14	Unitris Biopharma Co., Ltd	Intermediate for synthesizing caspofungin and preparation method therefor
CN106478781B (zh) *	2015-09-02	2020-04-07	正大天晴药业集团股份有限公司	卡泊芬净的制备方法
CN105440109B (zh) *	2015-11-26	2019-03-05	成都摩尔生物医药有限公司	一种卡泊芬净的制备方法
CN109721641B (zh) *	2017-10-31	2021-08-03	鲁南制药集团股份有限公司	一种卡泊芬净的合成方法
EP3620462A1 (fr) *	2018-09-04	2020-03-11	Xellia Pharmaceuticals ApS	Procédé de préparation de caspofungine

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US5202309A (en)	1989-06-30	1993-04-13	Merck & Co., Inc.	Antibiotic cyclopeptide fermentation product
US5194377A (en)	1989-06-30	1993-03-16	Merck & Co., Inc.	Antibiotic agent
US6030944A (en)	1991-10-01	2000-02-29	Merck & Co., Inc.	Cyclohexapeptidyl bisamine compounds
AU5354094A (en) *	1992-10-16	1994-05-09	Merck & Co., Inc.	An improved process for cyclohexapeptidyl bisamine compounds
US5378804A (en)	1993-03-16	1995-01-03	Merck & Co., Inc.	Aza cyclohexapeptide compounds
AU692043B2 (en) *	1994-08-23	1998-05-28	Merck & Co., Inc.	An improved process for preparing side chain derivatives of cyclohexapeptidyl lipopeptides
US5552521A (en)	1995-02-10	1996-09-03	Merck & Co., Inc.	Process for preparing certain aza cyclohexapeptides
HRP970318B1 (en)	1996-06-14	2002-06-30	Merck & Co Inc	A process for preparing certain aza cyclohexapeptides
US5936062A (en)	1997-06-12	1999-08-10	Merck & Co., Inc.	Process for preparing certain aza cyclohexapeptides
US5965612A (en) *	1997-08-22	1999-10-12	Merck & Co., Inc.	4-cyano-4-deformylsordaricin derivatives
US5972996A (en) *	1997-08-22	1999-10-26	Merck & Co., Inc.	4-cyano-4-deformylsordarin derivatives
WO2002055022A2 (fr) *	2001-01-09	2002-07-18	Merck & Co., Inc.	Metabolite actif de compose antifongique
AR035808A1 (es)	2001-04-12	2004-07-14	Merck & Co Inc	Proceso de deshidratacion capaz de minimizar la epimerizacion de un grupo hidroxilo por ciertas equinocandinas

2005
- 2005-11-15 EP EP05024961A patent/EP1785432A1/fr not_active Withdrawn
2006
- 2006-11-13 CA CA2626921A patent/CA2626921C/fr not_active Expired - Fee Related
- 2006-11-13 WO PCT/EP2006/010867 patent/WO2007057141A1/fr not_active Ceased
- 2006-11-13 DE DE602006007612T patent/DE602006007612D1/de active Active
- 2006-11-13 ES ES06818498T patent/ES2327962T3/es active Active
- 2006-11-13 PL PL06818498T patent/PL1951747T3/pl unknown
- 2006-11-13 BR BRPI0618591-6A patent/BRPI0618591A2/pt not_active IP Right Cessation
- 2006-11-13 EP EP06818498A patent/EP1951747B1/fr active Active
- 2006-11-13 DK DK06818498T patent/DK1951747T3/da active
- 2006-11-13 HR HR20090474T patent/HRP20090474T1/xx unknown
- 2006-11-13 US US12/093,657 patent/US20080319162A1/en not_active Abandoned
- 2006-11-13 PT PT06818498T patent/PT1951747E/pt unknown
- 2006-11-13 CN CN2006800422331A patent/CN101305018B/zh not_active Expired - Fee Related
- 2006-11-13 AT AT06818498T patent/ATE435233T1/de active
- 2006-11-13 JP JP2008540498A patent/JP4966314B2/ja not_active Expired - Fee Related
- 2006-11-13 SI SI200630411T patent/SI1951747T1/sl unknown
2008
- 2008-03-20 IL IL190333A patent/IL190333A/en not_active IP Right Cessation
- 2008-05-14 KR KR1020087011523A patent/KR101342304B1/ko not_active Expired - Fee Related

Also Published As

Publication number	Publication date
SI1951747T1 (sl)	2009-12-31
ATE435233T1 (de)	2009-07-15
KR20080069998A (ko)	2008-07-29
PL1951747T3 (pl)	2009-12-31
WO2007057141A1 (fr)	2007-05-24
HRP20090474T1 (hr)	2009-10-31
IL190333A (en)	2010-12-30
CN101305018A (zh)	2008-11-12
KR101342304B1 (ko)	2013-12-16
EP1785432A1 (fr)	2007-05-16
PT1951747E (pt)	2009-08-12
CA2626921A1 (fr)	2007-05-24
DE602006007612D1 (de)	2009-08-13
CN101305018B (zh)	2013-03-27
ES2327962T3 (es)	2009-11-05
US20080319162A1 (en)	2008-12-25
DK1951747T3 (da)	2009-10-12
EP1951747A1 (fr)	2008-08-06
JP2009515917A (ja)	2009-04-16
JP4966314B2 (ja)	2012-07-04
BRPI0618591A2 (pt)	2011-09-06
EP1951747B1 (fr)	2009-07-01

Publication	Publication Date	Title
CA2626921C (fr)	2013-09-17	Procede et intermediaires pour la synthese de la caspofungine
DK2694531T3 (en)	2016-12-12	METHODS OF MAKING of an antifungal agent
JPH04235196A (ja)	1992-08-24	ある種のシクロヘキサペプチドの還元法
JPH08509722A (ja)	1996-10-15	シクロヘキサペプチジルアミン化合物
JP2002504515A (ja)	2002-02-12	環状ペプチド抗真菌物質
EP1392722B1 (fr)	2009-04-08	Procede visant les echinocandines
JP2002535248A (ja)	2002-10-22	環式ペプチド抗真菌剤
AU2002256323A1 (en)	2003-04-17	Echinocandin process
CA2354055A1 (fr)	2000-06-22	Agents antifongiques de peptide cyclique possedant un substituant sucre
KR101331984B1 (ko)	2013-11-25	카스포펀진 제조방법 및 그의 신규 중간체
JPH10500141A (ja)	1998-01-06	シクロヘキサペプチジルリポペプチドの側鎖誘導体の改良製造方法
US20040158034A1 (en)	2004-08-12	Echinocandin process
WO1994009033A1 (fr)	1994-04-28	Procede ameliore de preparation de composes de bisamine cyclohexapeptidyle
WO2016091746A1 (fr)	2016-06-16	Procédé d'acylation d'un peptide cyclique
JP4493891B2 (ja)	2010-06-30	エキノカンジンの新誘導体、それらの製造方法及びそれらの抗菌剤としての使用
WO1998022498A1 (fr)	1998-05-28	Hexapeptides cycliques ayant une activite antibiotique
RU2575237C2 (ru)	2016-02-20	Способ изготовления противогрибкового агента
JP2000501076A (ja)	2000-02-02	シクロヘキサペプチジルビスアミン化合物、その化合物を含む組成物とその使用方法

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2017-12-26	MKLA	Lapsed	Effective date: 20171114